Diuretics Flashcards
(38 cards)
Main site of action for diuretics
lumenal (urine) surface of renal tubule cells
Mechanisms of diuretics
·Interactions with membrane transport proteins (thiazides, furosemide, triamterene) • Specific interactions with enzymes (acetazolamide) or hormone receptors (spironolactone) • Osmotic effects preventing water reabsorption (mannitol)
How do diuretics affect Na?
Do NOT act at Na/K pump. Diuretics decrease Na reabsorption
Which diuretics act at the proximal convoluted tubule?
Carbonic anhydrase inhibitors,
Which diuretics act at loop of Henle
High Ceiling Diuretics
Which diuretics act on distal convuluted tubule?
Thiazide diuretics
Which diuretics act on the collecting tubules?
Potassium sparing diuretics: Aldosterone antagonists and Na-channel blockers
Proximal convoluted tubule reabsorption
Almost all metabolites and 60-70% Na is reabsorbed here.
What does Carbonic anhydrase do and where is it located? -not on test
CA is on luminal surface of proximal convoluted tubule. Allows for reabsorption of HCO3- and exchanges H for Na (Na is reabsorbed and H is excreted into urine)
Carbonic anhydrase inhibitors- example and MOA -not on test
Acetazolamide. Inhibits CA enzyme
Carbonic anhydrase inhibitors-clinical uses and toxicities - not on test
Not used in HF. Used for glaucoma and acute mountain sickness (slow progression of pulmonary or cerebral edema). Toxicity: increased urinary pH, K+ wasting
Function of Loop of Henle
Water removal from lumen ccurs in descending limb. Active NaCl reabsorption occurs in ascending limb via Na-K-2CL cotransporter.
Loop of Henle agents (High ceiling diuretics)- examples
Furosemide, torsemide and bumetanide
High ceiling diuretics MOA
Inhibit NaCl transport (Na+-K+-2Cl–transporter) in thick ascending limb of loop of Henle. This results in increased Mg and Ca excretion into lumen to offset the lumen positive potential
High ceiling diuretics pharmacokinetics
Rapid oral absorption. Renal secretion and filtration
High ceiling diuretics clinical use in CHF
Preferred diuretic class b/c efficiency. Used in HF patients with volume overload to eliminate pulmonary congestion and peripheral edema. Enhanced with salt restrictions. Furosemide most commonly used.
Why do HF patients have reduced diuretic response?
decreased drug delivery to kidney due to decreased Renal Blood Flow and hypoperfusion activation of RAAS and SNS
Additional uses of high ceiling diuretics besides HF
Acute pulmonary edema, refractory edema, Hypercalcemia
Explain drug combos commonly used in refractory edema
High ceiling diuretic can be combined with Thiazide (blocks distal tubule Na reabsorption which is sometimes increased with high ceiling due to increased Na delivery to this segment), or Aldosterone antagonists to improve survival and ameliorate K wasting.
High ceiling diuretics adverse reactions
Hypokalemic metabolic alkalosis via enhanced secretion of K+ and H(can cause ectopic pacemakers), ototoxicity,Hyperuricemia/hyperglycemia, hypomagnesemia
Loop diuretic effect on plasma electrolytes- efficacy, K, H, Ca, Mg, Urate
high efficacy, decreased K, decreased H, decreased Ca, decreased Mg, increased urate
Function of distal convoluted tubule
Na/Cl co transporter facilitates reabsorption of NaCl. Also site of active Ca reabsorption via Na/Ca exchanger which is regulated by parathyroid hormone
Thiazide examples
Hydrochlorothiazide - Chlorthalidone - Metolazone
Thiazide MOA
inhibiting the Na+/Cl- cotransporter and increasing urinary excretion of NaCl (modest diuretic effect, only 5-10% of filtered Na+ is reabsorbed here). Increases reabsorption of Ca